Federal Register / Vol. 59,'No.->-127 / Tuesday,' July 5, 1994 / Notices 
34533 
Appendix M-IIl-D-l-a. Emphasize 
the issues related to gene marking, gene 
transfer, or gene therapy. 
Appendix M-lII-D-l-b. State 
explicitly whether the Points to 
Consider have been addressed 
satisfactorily. 
Appendix M-IlI-D-l-c. Examine the 
scientific rationale, scientific context 
(relative to other proposals reviewed by 
the RAC), whether the preliminary in 
vitro and in vivo data were obtained in 
appropriate models and are sufficient, 
and whether questions related to safety, 
efficacy, and social/ethical context have 
been resolved. 
Appendix M-III-D-l-d. Whenever 
possible, criticisms of Informed Consent 
documents should include written 
alternatives for suggested revisions for 
the RAC to consider. 
Appendix M-III-I>-l-e. Primary 
reviews should state whether the 
proposal is: (i) acceptable as written, (ii) 
expected to be acceptable with specific 
reWslons or after satisfactory responses 
to specific questions raised on review, 
or (iii) unacceptable in its present form. 
Appendix M-lll-D-2. Oral 
Discussions by Primary Reviewers at the 
RAC Meeting. Appendix M-IIl-D-2-a. It 
should be possible for most primary 
reviewers to present their oral reviews 
in ^ 5 minutes. 
Appendix M-IV. Reporting 
Requirements 
Appendix M-IV-A. Serious adverse 
effe^s of treatment should be reported 
inunediately to the local Institutional 
Review Board, the NIH Office for 
Protection from Research Risks, and 
NIH/ORDA followed by the submission 
of a written report filed with each 
group. Reports submitted to NIH/ORDA 
shall be sent to the Office of 
Recombinant DNA Activities, National 
Institutes of Health, Building 31, Room 
4B11, Bethesda, Maryland 20892, (301) 
49fi-9838. 
Appendix M-IV-B. Reports regarding 
the general progress of patients should 
be filed with both the local Institutional 
Review Board and NIH/ORDA within 
six months of the commencement of the 
experiment and at six-month Intervals 
thereafter. These twico-yearly reports 
should continue for a sufficient period 
of time to allow observation of all major 
effects. In the event of a patient’s death, 
a summary of the special post-mortem 
studies and statement of the cause of 
death should be submitted to the 
Institutional Review Board and NIH/ 
ORDA, if available. 
Appendix M-V. Procedures to the 
Followed for Accelerated Review of 
Human Gene Transfer Experiments by 
NIH/ORDA under Section lll-B-2 
Requests for Accelerated Review 
should be submitted to the Office of 
Recombinant DNA Activities, National 
Institutes of Health, Bethesda, Marj'land 
20892, (301) 496-9838. 
Appendix M-V-A. Human gene 
transfer experiments in this category 
must be in accordance with the 
provisions of Section lII-B-2. If the 
human gene transfer protocol does not 
qualify for Accelerated Review (see 
Section III-B-2) as determined by NIH/ 
ORDA, then the Principal Investigator 
must submit the experiment for Pall 
RAC review and NIH approval in 
accordance with Section III-A-2. 
Appendix M-V-B. No protocol shall 
be considered without Institutional 
Biosafety Committee and Institutional 
Review Board approval. 
Appendix M-V-C. At this time, all 
gene transfer protocols must be 
considered experimental. 
Appendix M-V-D. Principal 
Investigators requesting Accelerated 
Review (see Section III-B-2), must 
submit the relevant documentation in 
accordance with Appendix M-III. NIH/ 
ORDA will notify the Principal 
Investigator whether the proposed study 
qualifies for the Accelerated Review 
process. If NEH/ORDA determines that 
an experiment does not qualify for 
Accelerated Review process, the 
Principal Investigator must submit the 
proposal for full RAC review < 8 weeks 
prior to the next scheduled RAC 
meeting. 
Appendix M-V-E. It is expected that 
NIH/ORDA will consult with the RAC 
Chair and one or more RAC members, 
as necessary, when considering 
Accelerated Review human gene 
transfer protocols (see Section Ill-B-2). 
Appendix M-V-F. The RAC Chair 
will provide a report on all human gene 
transfer protocols that have been 
approved by NIH/ORDA at the next 
regularly scheduled RAC meeting. 
Appendix M-V-F-1. In accordance 
with Reporting Requirements (See 
Appendix M- IV), any adverse effects of 
the treatment should he reported 
immediately to the local institutional 
Review Board, the NIH Office for 
Protection from Research Risks, and 
NIH/ORDA followed by the submission 
of a written report filed with each 
group. Reports submitted to NIH/ORDA 
shall be sent to the Office of 
Recombinant DNA Activities, National 
Institutes of Health, Building 31 , Room 
4B11 , Bethesda, Maryland 20892, (301) 
496-9838. 
Appendix M-V-F-2. In accordance 
with Reporting Requirements (see 
Appendix M- IV), reports regarding the 
genera! progress of patients should be 
filed with both the local Institutional 
Review Board and NIH/ORDA within 
six months of the commencement of the 
experiment and at six-month intervals 
thereafter. In the event of a patient’s 
death, a summary of the special post- 
mortem studies and statement of the 
cause of death should be submitted to 
the Institutional Review Board and NTH/ 
ORDA, if available. 
Appendix M-VI. Procedures to be 
Followed for Expedited Review of 
Single Patient Human Gene Transfer 
Experiments by NIH Director Under 
Section HI- A-2 Requests for Expedited 
Review should be submitted to the 
Office of Recombinant DNA Activities, 
National Insitutes of Health, Bethesda, 
Maryland 20892, (301) 496-9838. 
App>endix M-VI-A. A Principal 
Investigator submitting a request to the 
NIH/ORDA for Expedited Review of a 
single patient gene transfer protocol 
shall provide detailed information 
regarding the necessity of Expedited 
Review. 
Appendix M-Vl-B. No protocol shall 
be considered without relevant 
Institutional Biosafety Committee and 
Institutional Review Board approvals. 
Appendix M-Vl-C At this time, all 
gene transfer protocols are considered 
experimental. 
Appendix M-VI-D. Regardless of the 
method of review, the Points to 
Consider is the standard of review for 
all gene transfer protocols. 
Appendix M-VI-E. Review of sucli 
protocols may include intramural NIH 
experts but must include extramural 
experts. 
Appendix M-VI-F. The reviewers 
shall consider similarity of the new 
protocol to previously approved 
protocols. 
Appendix M-Vl-G. The NIH/ORDA 
shall report to the RAC following 
Expedited Review and Include all of the 
materials on which the decision was 
based. The RAC shall formally review 
the protocol at its next scheduled 
meeting. Patient privacy shall be 
maintained. 
Appendix M-Vl-H. Protocols that are 
deferred or not approved by the RAC in 
its normal review process are not 
eligible for Expedited Review. No 
protocol shall have more than one 
patient approved under Expedited 
Review. 
Appendix M-Vl-I. As requested in 
the context of non-oxpedited review, 
none of the costs of the experimental 
-protocol shall be borne by the patient or 
the patient’s family. 
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